Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594626 | Bioorganic & Medicinal Chemistry Letters | 2012 | 6 Pages |
Abstract
A protein without natural binding functions was engineered to bind HIV-1 integrase. Phage display selections applied a library of variants based on the C-terminal domain of the eye lens protein human γS-crystallin. Multiple loop regions were altered to encode libraries with â3.6 Ã 1011 different variants. A crystallin variant, termed integrase binding protein-10 (IBP-10), inhibits integrase catalysis with nanomolar Ki values. IBP-10 interacts with the integrase C-terminal domain and inhibits integrase substrate affinity. This allosteric mechanism allows IBP-10 to inhibit drug-resistant integrase variants. The results demonstrate the applicability of the crystallin scaffold for the discovery of binding partners and enzyme inhibitors.
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Authors
Issa S. Moody, Shawn C. Verde, Cathie M. Overstreet, W. Jr., Gregory A. Weiss,